A scientist on the Florida
campus of The Scripps Research Institute has been awarded more than $700,000 by
the National Institute on Drug Abuse (NIDA), part of the National Institutes of
Health (NIH), to study and optimize newly discovered
compounds to combat cocaine addiction.

Thomas Bannister, an assistant professor in
the Department of Chemistry and associate scientific director in the
Translational Research Institute at Scripps Florida, is the principal
investigator for the five-year study. Chemists in the Bannister group
discovered the compounds as part of an effort to find new classes of molecules
capable of treating brain disorders.

“Long-term drug addiction can cause
biochemical changes in the brain of the drug user,” said Bannister.
“Unfortunately the changes can reinforce the addiction, making it much more
difficult to resist the urge to relapse. Animal studies suggest that there may
be ways to normalize the brain chemistry of long-term drug users and raise the
odds for a successful recovery.”

The Bannister lab’s hypothesis is that drugs
capable of selective interactions with a brain protein called the NOP receptor
will be beneficial in addiction therapy. The main hurdle in testing this
hypothesis has been that drugs known to interact with the NOP receptor also
interact with opioid receptors, where drugs such as morphine, Oxycontin®, and
Vicoden® act to provide both pain relief and unwanted addictive effects. Thus if
these drugs were used for treating cocaine addiction, they could simply cause a
different addiction, a trade-off that wouldn’t be particularly useful.

The key finding prompting the grant
application was new chemistry that gave molecules increased selectivity for the
NOP receptor over the opioid receptors.

“We found molecules that were biologically
specific, acting only at the NOP receptor and having no opiate effects,” said
Bannister. “We made these advances while receiving funding from a NIH/NIDA
one-year “economic stimulus” grant, in collaboration with Claes Wahlestedt and
co-workers at the University of Miami. Claes’s group used studies with mice to
show that our selective new compounds were not addictive. They also found that drug-adapted
mice, after taking one of our best lead molecules, consumed less cocaine than
untreated mice.”

While many more studies are needed to see if
such therapy can work in humans, the new grant represents a major step toward
that objective.

“This grant will allow us to optimize the
chemical and biological properties of these molecules and to extensively study
their effects in the brain,” said Bannister. “The long-term goal is to develop
an entirely new and effective method for treating cocaine addiction.”

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“There may be ways to normalize the brain
chemistry of long-term drug users and raise the odds for a successful
recovery,” says Thomas Bannister, an assistant professor in the Department of
Chemistry and associate scientific director in the Translational Research
Institute. (Photo by Randy Smith.)